Tetrahydrocurcumin alleviates di-(2-ethylhexyl) phthalate-induced adipose tissue dysfunction and testicular toxicity in adult mice: possible involvement of adiponectin-adipoR signaling in the testis

Widespread exposure to endocrine disruptors is associated with metabolic dysfunction and reproductive toxicity. Tetrahydrocurcumin (THC) has attracted attention as it offers protection against obesity and metabolic disorders due to its potent antioxidative and diverse biological properties but its influence and underlying mechanism of action on adipose tissue function and DEHP-induced testicular injury remain unknown. Our results showed that THC (100 mg kg^-1 day^-1) administration for 27 weeks enlarged adipocytes while attenuating macrophage infiltration and IL-6 expression in the adipose tissue of male C57BL/6J mice exposed to 5 mg kg^-1 day^-1 of DEHP. Moreover, THC ameliorated DEHP-induced deregulation of adiponectin but not leptin. DEHP caused testicular histological damage, spermatogenesis impairment, apoptosis, inflammation, and AGE, which were improved by THC. THC treatment elevated Nrf2/HO-1 and decreased Glut1 in interstitial Leydig cells, which may contribute to its beneficial effects on the testis. Our results further demonstrated that THC also ameliorated circulating adiponectin and testicular adipoR1-AMPK signaling, partially accounting for the improvement of DEHP-caused testicular dysfunction. The finding of this study revealed that THC is a promising candidate for improving adipose and testicular dysfunction caused by DEHP.